We have shown that the serum of patients with Guillain Barre Syndrome (GBS) contain antibodies (Ab) that can react with peripheral nerve myelin (PNM) and activate the complement system. Recently, we discovered that some of these Ab specifically react with a neutral glycolipid (NGL) of human PNM> These Ab that correlated with disease activity and mediated in vitro demyelination also cross-reacted with Forssman glycolipid, a common component of various infectious agents and some mammalian membranes. In this proposal, we will study the role of Ab to peripheral nerve antigens in the production of inflammatory demyelination of peripheral nerve (PN). Specifically, we propose: 1. To study the heterogeneity of antigens bound by anti-PNM Ab, 2. to determine the ability of these Ab to mediate in vitro demyelination as well as cytolysis of rodent Schwann cells. 3. To determine the specific epitopes on Forssman that can react with Ab from GBS patients and anti-Forssman Ab from patients with acute viral or bacterial infection without peripheral demyelination. 4. We will also determine the ability of afinity purified and mAb to demyelinate in vivo. 5. We will further explore whether stimulation of a complement receptor, CR2, on the surface of B cells of GBS and healthy subjects participates in anti-PNM/NGL Ab production. These problems will be explored using, in vitro Schwann cells and dorsal root ganglion cultures and various assays using fluid phase C1 fixation and HPTLC immune blots. Determination of the antigens bound by anti-PNM Ab including the neutral glycolipid, the antigen distribution on potential immune targets such as PNM and Schwann cells and the ability of these Ab to experimentally induce demyelination are all important issues which would expand our knowledge of the roles of Ab in the pathogenesis of a human disease.